Cefalo was a third round draft choice (#81 overall) of the Miami Dolphins in the 1978 NFL Draft. He would play six seasons for the Dolphins, including Super Bowls (XVII and XIX), earning a reputation as a sure-handed, dependable receiver. In Super Bowl XVII, Cefalo replaced receiver Nat Moore out as the result of an ankle injury. He proved to be one of Miami's few bright spots in a 27-17 loss to the Washington Redskins. He caught the team's only offensive touchdown and averaged 21 yards per catch. Cefalo's 76-yard touchdown reception from quarterback David Woodley still ranks as the fifth-longest in Super Bowl history.

Cefalo is currently the play-by-play man and "Voice of the Miami Dolphins" radio broadcast team and the host of South Florida's First News Program for WIOD. In March 2012, Cefalo's International launched their new food, wine, and travel radio show called - Cefalo's - Eat This Drink That Go!, which also airs on Clear Channel Communications at WIOD610 and 100.3FM in South Florida as well as nationally streamed on www.WIOD.com and IHeartRadio. He does regular sports analysis for the NFL Network and WIOD's sister station WINZ, the Sports Animal, which also carries the Miami Dolphins broadcast.

In 1988, Cefalo won an Emmy for his writing on the 24th Olympic Games. The National Sportscasters and Sportswriters Association named him Florida Sportscaster of the Year five times (1998, 2001–2004).

Cefalo co-hosted PM Magazine, AM South Florida, and hosted the syndicated game shows Trump Card, and Sports Snapshot (according to The Encyclopedia of TV Game Shows Volume 2). He is the only alumnus of Penn State to ever host a game show.

He currently resides in Miami Beach, Florida, with his wife Janice and three daughters: Mia, and twins Ava and Katie.

Cefalo is a well-known oenophile, with over 1,200 bottles in his personal wine cellar. His family has been in the wine business for several generations.[4] The Cefalo family has been involved in the making and selling of wine for the past 150 years. Jimmy's great grandfather was a wine maker and inn keeper in Central Italy. His grandfather came to this country in 1908. Michael Cefalo became a coal miner, land owner, and wine maker in Northeastern Pennsylvania. One of his 7 sons, Charlie, continued the tradition with a bonded Pennsylvania winery producing Italian varietals until his passing.

Cefalo's Wine Cellar began in 2002 with a 3400 square foot retail/liquor store located in South Miami. The store specialized in hard-to-find, highly allocated wines. In 2005, Jimmy Cefalo and Brenda Bassett formed their company, Cefalo's International, which continues to grow with the launch of their new food wine and travel show, Cefalo's - Eat This Drink That Go!, as well as serving as the Wine Ambassador for Martini & Rossi, owned by Bacardi.

Until it closed in October 2008, Cefalo's Wine Cellar was a 7,000 square foot facility that included several components - a historic bar (The Taurus, built in 1911), a retail wine store (Cefalo's Wine Cellar) with tasting room and a private membership wine cave serving 99 members, with their private lockers (Cefalo's Cave Club). For Cefalo's Cave Club, a ridge was found under the aquifer where 36 feet was dug to create a two story wine cave.

In 2007, Jimmy Cefalo received an Honorary Doctor of Business Administration in Food and Beverage Management from Johnson & Wales University.

In 2008, Jimmy Cefalo and Cefalo's International became the Wine Ambassador for Martini & Rossi, the wine/vermouth portfolio for Bacardi. In March 2012, Jimmy Cefalo and Brenda Bassett launched Cefalo's - Eat This Drink That Go!, a radio show dedicated to food, wine and travel on Clear Channel's WIOD610, covering South Florida from Palm Beach down to the Florida Keys and also streamed nationally through IHeartRadio and their websites www.WIOD.com and www.EatThisDrinkThatGo.com and www.JimmyCefalo.com.